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ARTICLE IN BRIEF

In one of the largest published reports on the influenza A pandemic of 2009, investigators reported that children with underlying neurological conditions were 6.5 times more likely to have seizures and other neurological complications from the H1N1 virus than those without a history of chronic illness.

Investigators who followed the 2009 influenza A (H1N1) pandemic in six major pediatric hospitals in Australia found that ten percent of the flu patients had serious neurological complications, including death. One of the largest published series from the 2009 influenza pandemic, the data underscore the need for more routine influenza vaccines to reduce the risk of infection and the possibility for neurological symptoms, the study authors conclude.

Reporting in the Oct. 2 Neurology, Robert Booy, MD, head of Clinical Research at the National of the National Centre for Immunisation [sic] Research and Surveillance of the University of Sydney in Australia, and more than a dozen colleagues from other institutions, set out on an active surveillance program from June to September of 2009 (the southern hemisphere winter) and identified 506 children under 15 with laboratory confirmed pandemic H1N1.

Among the findings, children with underlying neurological conditions were 6.5 times more likely to have seizures and other neurological complications from the H1N1 virus than those without a history of chronic illness. [See “More Study Data.”]

The majority of these reports focused on the most severe complications of encephalitis. In this study, seven children developed encephalitis or encephalopathy and one of these children died. The others recovered without apparent ongoing problems.

Australia has influenza vaccine recommendations in place but no mandated programs. About 10 percent of the population, mostly people with chronic medical problems, receive annual vaccinations. One state in Australia has routine vaccination programs in place and still only half of the population is vaccinated.

Dr. Booy said that a third of the children admitted did not have obvious signs of flu. Only 40 percent had the classic triad of symptoms: fever, runny nose and cough. Many had just one symptom.

This fact led Dr. Booy and his colleagues to think that a lot of these other cases would not have been identified as influenza and tested for H1N1. It is possible that many young children would have instead received a lumbar puncture to test for meningitis.

Of the 38 children with seizures, most were self-limiting without brain damage. One of the two children who died had neurological damage before hospitalization for influenza.

“If people think that you only should vaccinate unhealthy children you are wrong,” said Dr. Booy. He said that rapid diagnosis could lead to early isolation of hospital patients and mitigate these complications, as well as reduce the possibility of in-hospital spread. In the current study, four children (8.1 percent) were admitted to the hospital for another reason and later contracted flu.

In 2009, the specimens that were positive for influenza A were sent on to virology laboratories where they were further characterized. At initial intake at the hospital, 40.3 percent of the tests were rapid antigen positive, 3.9 percent direct immunofluorescence positive, 83.4 percent PCR positive and 2.4 percent were culture positive for influenza. The other specimens were further subtyped and confirmed by the state reference labs.

STUDY LIMITATIONS

Dr. Booy said that some of the limitations of the study may have led to skewed numbers. For instance, they did not include cases from district general hospitals and it is possible that the severe neurological complications detected at the major children's hospitals may over-represent the rate of neurological problems. Later in the pandemic, the hospital workload made it more difficult to do routine influenza testing. And finally the group has not done a follow-up of the children once they were discharged from the hospital to see if there were any long-term problems.

An Aug. 29 paper in Pediatrics looked at the rate of pre-existing neurological disorders among those children who died of influenza during the 2009 pandemic. According to the US Centers for Disease Control and Prevention (CDC), 336 children died. The CDC analyzed the data from state and local health departments and determined that 227 of those children had a pre-existing medical problem and 64 percent had a neurodevelopmental or neurological disorder, mostly cerebral palsy, intellectual disability or epilepsy.

Georgina Peacock, MD, MPH, a medical officer and developmental-behavioral pediatrician with the Prevention Research Branch in the CDC's National Center on Birth Defects and Developmental Disabilities, said that children with underlying neurological disorders should receive influenza vaccine and be treated early and aggressively if they show signs of influenza.

“We need to pay close attention to these children,” she said. The most common neurological conditions were cerebral palsy, moderate to severe epilepsy and hydrocephalus. Ninety-four percent had neurodevelopmental problems and 51 percent had a history of epilepsy. The median age of these children was 10-years old. There were an equal number of males and females.

EXPERTS COMMENT

Dr. Peacock recommends that everyone over six months of age should be vaccinated against the flu. “It is good prevention,” she said. Her agency is trying to figure out the best way to educate families about the importance of influenza vaccines, especially when a child has a pre-existing neurological condition.

“This is an important paper,” said Avindra Nath, MD, clinical director of the National Institute of Neurological Disorders and Stroke and chief of the section of Infections of the Nervous System. “We know that the brains of young children are more vulnerable. Vaccinations can certainly help reduce these neurological symptoms.”

MORE STUDY DATA

* 49 (9.7 percent) had neurological complications, most commonly seizures. Over half of the children with neurological signs had a pre-existing medical condition and 42.8 percent had a pre-existing neurological disorder.

* After seizure, which was noted in 7.5 percent of the H1N1 cases, 1.4 percent of the children suffered encephalitis/encephalopathy, 1 percent confusion/disorientation, 1 percent loss of consciousness, and 0.4 percent paralysis/Guillain-Barre syndrome.

* Almost a third of the group (30.6 percent) with neurological symptoms was admitted to the ICU and a quarter of these children needed mechanical ventilation. Two children died. Both had a pre-existing health condition.

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